Subcutaneous Infliximab in Refractory Crohn’s Disease Patients: A Possible Biobetter?

Abstract

Background A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease (IBD) may offer improved efficacy versus intravenous infliximab (IFX-IV). Methods Patients with refractory Crohn’s disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study’s primary endpoint was the treatment’s persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment. Results Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 μg/ml at W30, whereas median ATI levels significantly declined. Among ATInegative patients at W0 (n = 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATIpositive patients at W0, ATI seroconversion from ATIpositive to ATInegative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein (p = .0341), fecal calprotectin (p = .0002), and Harvey-Bradshaw index (p = .0029) since W0. Conclusion Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX.

Switching from Intravenous to Subcutaneous Biological Therapy for Inflammatory Bowel Disease Patients Remains a Challenge

“…Cerna et al proposed that SC infliximab may be a “Biobetter”, aiming to improve upon existing biologics therapies. They suggested that, due to its low immunogenicity, SC infliximab can be used to reinduce therapy in refractory CD patients with positive neutralizing anti-infliximab antibodies [ 8 ]. Other real-world data further substantiate the evidence for both infliximab and vedolizumab [ 6 , 7 , 20 ].…”

“…In light of recent publications underscoring the safety and efficacy of SC administration of medications that are suitable for IBD maintenance via both the IV and SC routes [ 4 , 5 , 6 , 7 , 8 , 9 ], and considering the significantly higher costs associated with IV delivery [ 10 ], it is unequivocally in the best interest of the health system to accelerate the transition toward SC administration. The current trend of starting maintenance therapy with SC regimens implies that SC delivery will soon be the primary mode of treatment.…”